EP1087750A1 - Pharmaceutical formulations for aerosols with two or more active substances - Google Patents
Pharmaceutical formulations for aerosols with two or more active substancesInfo
- Publication number
- EP1087750A1 EP1087750A1 EP99928458A EP99928458A EP1087750A1 EP 1087750 A1 EP1087750 A1 EP 1087750A1 EP 99928458 A EP99928458 A EP 99928458A EP 99928458 A EP99928458 A EP 99928458A EP 1087750 A1 EP1087750 A1 EP 1087750A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- pharmaceutical preparation
- preparation according
- acid
- active substances
- stabiliser
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/12—Aerosols; Foams
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/008—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/12—Mucolytics
Definitions
- the present invention relates to new pharmaceutical formulations for aerosols with at least two or more active substances for use by inhalation or by the nasal route.
- the active substances can be formulated as solutions or suspensions.
- the vast majority of aerosol formulations for MDI ' s are prepared as suspensions, especially if the preparation contains more than one active substance.
- Formulations in the form of solutions are used only to a limited extent. In these cases, the formulations normally contain only one active substance.
- the chemical stability of the active substances is noticeably higher than in a solution. Additionally, in a suspension the active substance can be more highly concentrated than in a solution, with the result that suspension type formulation enable higher doses to be administered.
- a major disadvantage of suspension- formulations is the fact that over time (e.g. during storage) the suspended particles clump together to form bigger, more or less stable agglomerates or form loose flakes, sediments or floating layers, or in the worst case, particle growth, which significantly impairs the pharmaceutical quality of the product.
- the size of the particles formed or the speed of particle growth are influenced by the solubility features of the liquid phase.
- ingress of humidity during storage or a desired increase in polarity e.g. achieved by adding co- solvents, can have a devastating effect on the quality of the medical end product, particularly if the suspended particles have polar structure elements.
- the suspension can be physically stabilised by the addition of surfactants, by reducing the harmful effects of moisture and/or particle growth so that suspended particles can be held in suspension for longer.
- CFCs such as the above-mentioned TG 11, for example, have often been used as propellants.
- CFCs have been linked with the destruction of the ozone layer, their manufacture and use are being phased out. The intention is to replace them with special fluorohydrocarbons (HFC) which are less destructive to the ozone layer but have completely different solubility features.
- HFC fluorohydrocarbons
- the toxicological profile and physico-chemical properties such as the steam pressure, for example, determine which HFCs are suitable for MDIs.
- the most promising representatives at present are TG 134a (1,1,2,2- tetrafluoroethane) and TG 227 (1,1,1,2,3,3,3- heptafluoropropane) .
- aerosol formulations with two or more active substances.
- the active substances are formulated in the necessary concentrations as solutions or suspensions, frequently giving rise to problems regarding the chemical stability of the individual substances or the degree of concentration which can be attained.
- Major problems are encountered if one of the active substances cannot be suspended or is unstable in a suspension-type formulation of this kind or if one of the active substances is chemically unstable or will not dissolve in a solution- type formulation of this kind, particularly when HFC is used as the propellant.
- the invention relates to stable aerosol formulations with fluorohydrocarbons as propellants, particularly TG 134a and/or TG 227, consisting of two or more active substances, wherein at least one active substance is formulated as a solution and at least one active substance is formulated as a suspension.
- the pharmaceutical preparation according to the invention is used for inhalative treatment, particularly for treating diseases of the pharynx and respiratory tract, e.g. asthmatic diseases and COPD .
- a medicinally useful combination of two or more active substances containing beclometasone, budesonide, cromoglycinic acid, fenoterol, flunisolide, fluticasone, ipratropium bromide, nedocromil, orciprenaline, oxitropium bromide, reproterol, salbutamol (albuterol) , salmeterol, terbutalin, N- [ [2 , 2 -dimethyl-4- (2-oxo-2H-pyridin-l-yl) -6-trifluoromethyl-2H-l-benzopyran- 3 -yl] methyl] -N-hydroxy-acetamide, the esters, salts and/or solvates thereof.
- Which of the above-mentioned active substances is formulated as a solution and which as a suspension in the preparation according to the invention depends on the particular combinations of active substance and can be determined relatively quickly by solution and suspension trials.
- one or more of the following active substances are suspended: budesonide, cromoglycinic acid, nedocromil, reproterol and/or salbutamol (albuterol) or the esters, salts and/or solvates derived from these compounds and one or more of the following substances are dissolved: beclomethasone, fenoterol, ipratropium bromide, orciprenaline and/or oxitropium bromide, N- [ [2 , 2 -dimethyl - 4- (2-oxo-2H-pyridin-l-yl) -6-trifluoromethyl-2H-l- benzopyran-3-yl] methyl] -N-hydroxy-acetamide or the esters, salts and/or solvates derived from these compounds.
- Embodiments having two different active substances are preferred.
- a particularly preferred embodiment contains dissolved ipratropium bromide, particularly combined with salbutamol sulphate (albuterol sulphate) as the suspended active substance .
- the active substances are used in a therapeutically effective quantity, i.e. in a quantity that can induce a successful treatment.
- concentration of the active substances and the volume per stroke of spray are adjusted in such a way that the quantity of active substance which is medically necessary or recommended is released by a single spray or by a few sprays .
- One embodiment relates to formulations in which the suspended particles are stabilised by the addition of surfactant substances (surfactants) or other suspension- stabilising agents to stabilise the suspended particles against physical changes.
- surfactant substances surfactants
- the particle size will remain pharmaceutically acceptable even over lengthy periods, e.g. during storage.
- Preferred particle sizes are up to 20 ⁇ m, whilst particularly preferred particle sizes are between 5 and 15 ⁇ m, best of all not exceeding 10 ⁇ m.
- the advantage of these particle sizes is that the particles are small enough to penetrate deeply into the lungs but not so small as to be breathed out again with the exchanged air.
- Suitable surfactants and suspension- stabilising agents include all pharmacologically acceptable substances which have a lipophilic hydrocarbon group and one or more functional hydrophilic groups, especially C 5 _ 20 fatty alcohols, C 5 _ 20 fatty acids, C 5 _ 20 fatty acid esters, lecithin, glycerides, propyleneglycol esters, polyoxyethylenes, polysorbates , sorbitan esters and/or carbohydrates.
- C 5 . 20 fatty acids, propyleneglycol diesters and/or triglycerides and/or sorbitans of the C 5 _ 20 fatty acids are preferred, whilst oleic acid and sorbitan mono-, di- or trioleates are particularly preferred.
- toxicologically and pharmaceutically acceptable polymers and block-polymers can be used as suspension-stabilising agents.
- the surfactants used are either non-fluorinated or partially fluorinated or perfluorinated, the term fluorinated referring to the exchange of hydrogen radicals bound to the carbon for fluorine radicals.
- the quantity of surfactant may be up to 1 : 1 based on the proportion by weight of the suspended active substances; amounts of 0.0001:1 to 0.5:1 are preferred, whilst amounts of from 0.0001:1 to 0.25:1 are particularly preferred.
- a further advantage of the above surfactants is that they can also be used as valve lubricants. Therefore, one embodiment relates to formulations in which said surfactants are added as valve lubricants.
- the solubility of at least one active substance to be dissolved is increased by the addition of one or more co-solvents.
- This has the advantage that the active substance or substances to be dissolved can be formulated in higher concentrations.
- the addition of co-solvent must not exceed the critical threshold of polarity of the liquid phase at which one of the disadvantages described above begins to affect the suspended particles of active substance.
- Suitable co-solvents are pharmacologically acceptable alcohols such as ethanol, esters or water or mixtures thereof; ethanol is preferred.
- concentration of the co-solvent in relation to the total formulation may be from 0.0001 to 50 wt.-%, preferably 0.0001 to 25 wt.-%. In another embodiment a concentration of 0.0001 to 10 wt.-% is preferred whilst particularly preferred embodiments are those wherein just enough alcohol is added to dissolve the active substance which has to be dissolved.
- HFC propellants are added to the HFC propellant.
- These added propellants may be, beside other HFCs , saturated lower hydrocarbons such as propane, butane, isobutane or pentane provided that the mixture is pharmacologically acceptable.
- stabilisers are added to the formulation, with a beneficial effect on the pharmaceutical stability of the active substances even over lengthy periods, e.g. during storage.
- stabilisers denotes those substances which prolong the durability and usability of the pharmaceutical preparation by preventing or delaying chemical changes in the individual ingredients, particularly the active substances, e.g. caused by subsequent reactions or degradation, or those which prevent biological contamination.
- Stabilisers which are preferred for this purpose are those which influence the pH of the liquid phase, such as acids and/or the salts thereof, particularly suitable substances are hydrochloric acid, sulphuric acid, nitric acid, phosphoric acid, ascorbic acid, citric acid and the salts thereof.
- preferred bactericides, fungicides etc. are benzalkonium chloride or ethylene diamine tetraacetate . Citric acid is most preferred.
- the concentration of the stabilisers may be up to 1000 ppm, preferably up to 100 ppm and most preferably 20 to 40 ppm.
- One particularly preferred embodiment comprises suspended salbutamol sulphate (albuterol sulphate) , dissolved ipratropium bromide, ethanol as co-solvent and citric acid as stabiliser.
- Disodium chromoglycate is suspended in liquefied P134 and a small amount of ethanol and fenoterol hydrobromide is dissolved therein.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Emergency Medicine (AREA)
- Dispersion Chemistry (AREA)
- Otolaryngology (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
SI9930489T SI1087750T1 (en) | 1998-06-18 | 1999-06-08 | Pharmaceutical formulations for aerosols with two or more active substances |
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE1998127178 DE19827178A1 (en) | 1998-06-18 | 1998-06-18 | Stable aerosol formulations containing two or more bioactives used for pharmaceuticals |
DE19827178 | 1998-06-18 | ||
DE19842963 | 1998-09-19 | ||
DE1998142963 DE19842963A1 (en) | 1998-09-19 | 1998-09-19 | Stable aerosol formulations containing two or more bioactives used for pharmaceuticals |
PCT/US1999/012785 WO1999065464A1 (en) | 1998-06-18 | 1999-06-08 | Pharmaceutical formulations for aerosols with two or more active substances |
Publications (2)
Publication Number | Publication Date |
---|---|
EP1087750A1 true EP1087750A1 (en) | 2001-04-04 |
EP1087750B1 EP1087750B1 (en) | 2003-11-12 |
Family
ID=26046888
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP99928458A Expired - Lifetime EP1087750B1 (en) | 1998-06-18 | 1999-06-08 | Pharmaceutical formulations for aerosols with two or more active substances |
Country Status (33)
Country | Link |
---|---|
EP (1) | EP1087750B1 (en) |
JP (1) | JP2003522102A (en) |
KR (1) | KR100600423B1 (en) |
CN (1) | CN1161104C (en) |
AR (1) | AR019690A1 (en) |
AT (1) | ATE253896T1 (en) |
AU (1) | AU759222B2 (en) |
BG (1) | BG65252B1 (en) |
BR (1) | BR9911351A (en) |
CA (1) | CA2335065C (en) |
CO (1) | CO5070580A1 (en) |
CZ (1) | CZ300910B6 (en) |
DE (1) | DE69912781T2 (en) |
DK (1) | DK1087750T3 (en) |
EE (1) | EE04450B1 (en) |
ES (1) | ES2211108T3 (en) |
HK (1) | HK1037974A1 (en) |
HR (1) | HRP20000867B1 (en) |
HU (1) | HU229064B1 (en) |
ID (1) | ID27554A (en) |
IL (2) | IL140353A0 (en) |
ME (1) | ME00838B (en) |
MY (1) | MY121073A (en) |
NO (1) | NO329416B1 (en) |
NZ (1) | NZ509418A (en) |
PL (1) | PL193695B1 (en) |
PT (1) | PT1087750E (en) |
RS (1) | RS49977B (en) |
RU (1) | RU2218152C2 (en) |
SK (1) | SK284756B6 (en) |
TR (1) | TR200003721T2 (en) |
TW (1) | TW528606B (en) |
WO (1) | WO1999065464A1 (en) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
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EP2077132A1 (en) | 2008-01-02 | 2009-07-08 | Boehringer Ingelheim Pharma GmbH & Co. KG | Dispensing device, storage device and method for dispensing a formulation |
WO2010105776A1 (en) | 2009-03-17 | 2010-09-23 | Boehringer Ingelheim International Gmbh | Dispensing device, storage device and method for dispensing a formulation |
US7897617B2 (en) | 1999-07-14 | 2011-03-01 | Almirall Prodesfarma S.A. | Quinuclidine derivatives and medicinal compositions containing the same |
US8044205B2 (en) | 2006-07-21 | 2011-10-25 | Laboratorios Almirall, S.A. | Process for manufacturing 3(R)-(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane bromide |
US10085974B2 (en) | 2008-03-13 | 2018-10-02 | Almirall, S.A. | Dosage and formulation |
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GB9616237D0 (en) | 1996-08-01 | 1996-09-11 | Norton Healthcare Ltd | Aerosol formulations |
GB2332372B (en) * | 1997-12-08 | 2002-08-14 | Minnesota Mining & Mfg | Pharmaceutical aerosol compositions |
DZ2947A1 (en) | 1998-11-25 | 2004-03-15 | Chiesi Farma Spa | Pressure metered dose inhaler. |
US7214687B2 (en) | 1999-07-14 | 2007-05-08 | Almirall Ag | Quinuclidine derivatives and medicinal compositions containing the same |
IT1313553B1 (en) | 1999-07-23 | 2002-09-09 | Chiesi Farma Spa | OPTIMIZED FORMULATIONS CONSTITUTED BY SOLUTIONS OF STEROIDS GIVEN BY INHALATION. |
AU7026800A (en) | 1999-09-11 | 2001-04-17 | Glaxo Group Limited | Pharmaceutical formulation of fluticasone propionate |
JP2003514841A (en) * | 1999-11-23 | 2003-04-22 | グラクソ グループ リミテッド | Pharmaceutical formulations of salmeterol |
ES2238334T3 (en) * | 1999-12-24 | 2005-09-01 | Glaxo Group Limited | PHARMACEUTICAL FORMULATION IN SALMETEROL AEROSOL AND FLUTICASONA PROPIONATE. |
IT1317846B1 (en) | 2000-02-22 | 2003-07-15 | Chiesi Farma Spa | FORMULATIONS CONTAINING AN ANTICOLINERGIC DRUG FOR THE TREATMENT OF CHRONIC OBSTRUCTIVE BRONCOPNEUMOPATHY. |
GB0008485D0 (en) * | 2000-04-07 | 2000-05-24 | Glaxo Group Ltd | Pharmaceutical compositions |
IL152955A0 (en) | 2000-05-22 | 2003-06-24 | Chiesi Farma Spa | Stable pharmaceutical solution formulations for pressurised metered dose inhalers |
DE10062712A1 (en) * | 2000-12-15 | 2002-06-20 | Boehringer Ingelheim Pharma | New drug compositions based on anticholinergics and corticosteroids |
US20030055026A1 (en) | 2001-04-17 | 2003-03-20 | Dey L.P. | Formoterol/steroid bronchodilating compositions and methods of use thereof |
DE10130371A1 (en) * | 2001-06-23 | 2003-01-02 | Boehringer Ingelheim Pharma | New drug compositions based on anticholinergics, corticosteroids and betamimetics |
EP1661570A3 (en) | 2001-09-18 | 2012-10-24 | Nycomed Danmark ApS | Compositions comprising ipatropium and xylometazoline for treatment of the common cold |
JP2010184937A (en) * | 2001-10-26 | 2010-08-26 | Dey Lp | Albuterol and ipratropium inhalation solution for relieving symptom of chronic obstructive pulmonary disease, kit, method for preparing one vessel containing the inhalation solution and method for preparing the inhalation solution |
GB0207899D0 (en) * | 2002-04-05 | 2002-05-15 | 3M Innovative Properties Co | Formoterol and cielesonide aerosol formulations |
EP1915985A1 (en) * | 2003-03-20 | 2008-04-30 | Boehringer Ingelheim Pharmaceuticals Inc. | Formulation for a Metered Dose Inhaler Using Hydro-Fluoro-Alkanes as Propellants |
TWI359675B (en) | 2003-07-10 | 2012-03-11 | Dey L P | Bronchodilating β-agonist compositions |
US9308199B2 (en) * | 2004-04-29 | 2016-04-12 | Honeywell International Inc. | Medicament formulations |
EP1595531A1 (en) | 2004-05-13 | 2005-11-16 | CHIESI FARMACEUTICI S.p.A. | Stable pharmaceutical solution formulations for pressurized metered dose inhalers |
JP2008546634A (en) * | 2005-03-16 | 2008-12-25 | ハネウェル・インターナショナル・インコーポレーテッド | Pharmaceutical delivery formulations, devices and methods |
DE102006053374A1 (en) * | 2006-02-09 | 2007-08-16 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Pharmaceutical formulation for aerosols with two or more active substances and at least one surface-active substance |
DE102006017320A1 (en) | 2006-04-11 | 2007-10-18 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Aerosol suspension formulations with TG 227 ea or TG 134 a as propellant |
US8061350B2 (en) | 2006-06-02 | 2011-11-22 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Process and device for dosing pharmaceutical agents |
US20070286814A1 (en) * | 2006-06-12 | 2007-12-13 | Medispray Laboratories Pvt. Ltd. | Stable aerosol pharmaceutical formulations |
EP2100598A1 (en) | 2008-03-13 | 2009-09-16 | Laboratorios Almirall, S.A. | Inhalation composition containing aclidinium for treatment of asthma and chronic obstructive pulmonary disease |
JP5670421B2 (en) | 2009-03-31 | 2015-02-18 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Component surface coating method |
JP5763053B2 (en) | 2009-05-18 | 2015-08-12 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Adapter, inhaler and atomizer |
AU2010323220B2 (en) | 2009-11-25 | 2015-04-23 | Boehringer Ingelheim International Gmbh | Nebulizer |
EP2504051B1 (en) | 2009-11-25 | 2019-09-04 | Boehringer Ingelheim International GmbH | Nebulizer |
US10016568B2 (en) | 2009-11-25 | 2018-07-10 | Boehringer Ingelheim International Gmbh | Nebulizer |
WO2011084316A2 (en) | 2009-12-16 | 2011-07-14 | 3M Innovative Properties Company | Formulations and methods for controlling mdi particle size delivery |
EP2585151B1 (en) | 2010-06-24 | 2018-04-04 | Boehringer Ingelheim International GmbH | Nebulizer |
WO2012130757A1 (en) | 2011-04-01 | 2012-10-04 | Boehringer Ingelheim International Gmbh | Medical device comprising a container |
EP2510928A1 (en) | 2011-04-15 | 2012-10-17 | Almirall, S.A. | Aclidinium for use in improving the quality of sleep in respiratory patients |
US9827384B2 (en) | 2011-05-23 | 2017-11-28 | Boehringer Ingelheim International Gmbh | Nebulizer |
WO2013152894A1 (en) | 2012-04-13 | 2013-10-17 | Boehringer Ingelheim International Gmbh | Atomiser with coding means |
EP2835146B1 (en) | 2013-08-09 | 2020-09-30 | Boehringer Ingelheim International GmbH | Nebulizer |
WO2015018904A1 (en) | 2013-08-09 | 2015-02-12 | Boehringer Ingelheim International Gmbh | Nebulizer |
US10722666B2 (en) | 2014-05-07 | 2020-07-28 | Boehringer Ingelheim International Gmbh | Nebulizer with axially movable and lockable container and indicator |
JP6526057B2 (en) | 2014-05-07 | 2019-06-05 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Nebulizer and container |
HUE064131T2 (en) | 2014-05-07 | 2024-03-28 | Boehringer Ingelheim Int | Unit, nebulizer and method |
WO2020152548A1 (en) * | 2019-01-24 | 2020-07-30 | Glenmark Pharmaceuticals Limited | Stable aerosol inhalation compositions of formoterol |
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-
1999
- 1999-06-08 KR KR1020007014407A patent/KR100600423B1/en not_active IP Right Cessation
- 1999-06-08 RU RU2001101898/15A patent/RU2218152C2/en active
- 1999-06-08 RS YUP-800/00A patent/RS49977B/en unknown
- 1999-06-08 WO PCT/US1999/012785 patent/WO1999065464A1/en active IP Right Grant
- 1999-06-08 PL PL99345685A patent/PL193695B1/en unknown
- 1999-06-08 IL IL14035399A patent/IL140353A0/en active IP Right Grant
- 1999-06-08 PT PT99928458T patent/PT1087750E/en unknown
- 1999-06-08 AU AU45521/99A patent/AU759222B2/en not_active Expired
- 1999-06-08 DK DK99928458T patent/DK1087750T3/en active
- 1999-06-08 AT AT99928458T patent/ATE253896T1/en active
- 1999-06-08 SK SK1939-2000A patent/SK284756B6/en unknown
- 1999-06-08 NZ NZ509418A patent/NZ509418A/en not_active IP Right Cessation
- 1999-06-08 ID IDW20002641A patent/ID27554A/en unknown
- 1999-06-08 DE DE69912781T patent/DE69912781T2/en not_active Expired - Lifetime
- 1999-06-08 BR BR9911351-1A patent/BR9911351A/en not_active Application Discontinuation
- 1999-06-08 EE EEP200000759A patent/EE04450B1/en unknown
- 1999-06-08 EP EP99928458A patent/EP1087750B1/en not_active Expired - Lifetime
- 1999-06-08 ME MEP-2000-800A patent/ME00838B/en unknown
- 1999-06-08 ES ES99928458T patent/ES2211108T3/en not_active Expired - Lifetime
- 1999-06-08 CN CNB99807439XA patent/CN1161104C/en not_active Expired - Lifetime
- 1999-06-08 TR TR2000/03721T patent/TR200003721T2/en unknown
- 1999-06-08 CA CA002335065A patent/CA2335065C/en not_active Expired - Lifetime
- 1999-06-08 HU HU0104734A patent/HU229064B1/en unknown
- 1999-06-08 JP JP2000554344A patent/JP2003522102A/en active Pending
- 1999-06-08 CZ CZ20004750A patent/CZ300910B6/en not_active IP Right Cessation
- 1999-06-15 TW TW088110010A patent/TW528606B/en not_active IP Right Cessation
- 1999-06-16 MY MYPI99002491A patent/MY121073A/en unknown
- 1999-06-17 CO CO99037969A patent/CO5070580A1/en unknown
- 1999-06-18 AR ARP990102935A patent/AR019690A1/en active Pending
-
2000
- 2000-12-07 BG BG105033A patent/BG65252B1/en active Active
- 2000-12-12 NO NO20006318A patent/NO329416B1/en not_active IP Right Cessation
- 2000-12-15 HR HR20000867A patent/HRP20000867B1/en not_active IP Right Cessation
- 2000-12-15 IL IL140353A patent/IL140353A/en not_active IP Right Cessation
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2001
- 2001-12-19 HK HK01108873A patent/HK1037974A1/en unknown
Non-Patent Citations (1)
Title |
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See references of WO9965464A1 * |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7897617B2 (en) | 1999-07-14 | 2011-03-01 | Almirall Prodesfarma S.A. | Quinuclidine derivatives and medicinal compositions containing the same |
US8129405B2 (en) | 1999-07-14 | 2012-03-06 | Almirall Prodesfarma S.A. | Quinuclidine derivatives and medicinal compositions containing the same |
US9687478B2 (en) | 1999-07-14 | 2017-06-27 | Almirall, S.A. | Quinuclidine derivatives and medicinal compositions containing the same |
US10588895B2 (en) | 1999-07-14 | 2020-03-17 | Almirall, S.A. | Quinuclidine derivatives and medicinal compositions containing the same |
US8044205B2 (en) | 2006-07-21 | 2011-10-25 | Laboratorios Almirall, S.A. | Process for manufacturing 3(R)-(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane bromide |
EP2077132A1 (en) | 2008-01-02 | 2009-07-08 | Boehringer Ingelheim Pharma GmbH & Co. KG | Dispensing device, storage device and method for dispensing a formulation |
US10085974B2 (en) | 2008-03-13 | 2018-10-02 | Almirall, S.A. | Dosage and formulation |
WO2010105776A1 (en) | 2009-03-17 | 2010-09-23 | Boehringer Ingelheim International Gmbh | Dispensing device, storage device and method for dispensing a formulation |
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